In vivo dGEMRIC was validated in two ways: First, patients were imaged before total knee replacement surgery; the joint was then obtained for ex-vivo dGEMRIC (already validated against histology), and then with histology directly. An example is shown in Figure 1. Secondly, a dGEMRIC image was taken with the regular Gd(DTPA)2- contrast agent, and then repeated (within a week or so) with a non-ionic contrast agent GdHPDO3A. The two contrast agents have similar MW. The uniform distribution of the non-ionic contrast agent provides further evidence that the non-homogeneous distribution of the ionic contrast agent (Figure 2) is due to the distribution of charge, or GAG concentration in the tissue.

In vivo
invivovalidgrad invivovalidex

Figure 1: In vivo dGEMRIC color coded image of GAG compared with excised dGEMRIC image and histology.

Ionic contrast agent
Non-Ionic contrast agent
Figure 2: dGEMRIC (Gd(DTPA)2-) image vs. an image obtained with a non-ionic contrast agent (GdHPDO3A). The non-ionic contrast agent distributes uniformly in the cartilage.

For further details on these studies, please refer to:

  • Bashir A, Gray ML, Boutin R, Burstein D. In vivo imaging of GAG in articular cartilage using delayed Gd(DTPA)2- enhanced MRI. Radiology 1997; 205: 551-558.
  • Bashir A, Gray ML, Hartke J, Burstein D. Nondestructive Imaging of Human Cartilage Glycosaminoglycan Concentration by MRI. Magn Reson Med 1999; 41:857-865.

The final in vivo protocol is discussed in:

  • Burstein D, Velyvis JH, Scott KT, Stock KW, Kim YJ, Jaramillo D, Boutin RD, Gray ML. Protocol issues for delayed Gd(DTPA)2- enhanced MR imaging (dGEMRIC) for clinical evaluation of cartilage. Magn Reson Med 2001; 45:36-41.